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Deconvolution Analysis of Rapid Insulin Pulses before and after Six Weeks of Continuous Subcutaneous Administration of Glucagon-Like Peptide-1 in Elderly Patients with Type 2 Diabetes

Division of Geriatric Medicine (G.S.M.), Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4E3; Department of Medicine (J.D.V.), Mayo Clinic, Rochester, Minnesota 55905; and Department of Surgery (D.E.), University of Massachusetts Medical School, Worcester, Massachusetts 01655

Address all correspondence and requests for reprints to: Dariush Elahi, Ph.D., Department of Surgery, Endocrinology and Metabolism Laboratory, University Campus, 55 Lake Avenue North, Worcester, Massachusetts 01655. E-mail: dariush.elahi{at}umassmed.edu.

Context: Insulin is secreted in a pulsatile fashion with measurable orderliness (low entropy). Normal aging and diabetes in middle-aged patients is characterized by alterations in pulsatile insulin release.

Objectives: We undertook the current studies to determine whether disruptions in pulsatile insulin release also accompany diabetes in the elderly.

Design: Two studies were performed. In the first study, insulin values were sampled every minute for 1 h under fasting conditions. In the second study, subjects underwent a 2-h hyperglycemic glucose clamp (glucose 5.4 mM above basal). From 60–120 min, insulin was sampled every 1 min. Secretory pulse analysis was conducted using a multiparameter deconvolution technique.

Setting: The study was conducted in a general clinical research center and during outpatient visits.

Patients: Volunteers were healthy young [n = 10; body mass index (BMI), 23 ± 1 kg/m²; age, 23 ± 1 yr] and elderly (n = 10; BMI, 24 ± 1 kg/m²; age, 78 ± 2 yr) volunteers and elderly patients with diabetes (n = 8; BMI, 28 ± 1 kg/m²; age, 73 ± 2 yr).

Intervention: Five of the older patients with type 2 diabetes (BMI, 29 ± 1 kg/m²; age, 72 ± 2 yr) were treated with continuous sc glucagon-like peptide-1 (GLP-1) (7–36) amide infusion for 6 wk, and a second 2-h hyperglycemic clamp was performed.

Main Outcome Measures: Insulin burst mass, pulsatile insulin secretion, and entropy were measured.

Results: Under fasting conditions, elderly patients with diabetes had a reduction in insulin burst mass (P < 0.05) that was similar to normal elderly. During hyperglycemia, elderly patients with diabetes had an even greater impairment in insulin burst mass (P < 0.05) and basal (P < 0.05) and pulsatile insulin secretion (P < 0.05) than normal elderly. Approximate entropy, a measure of irregularity of insulin release, was increased to a greater extent in older diabetes patients than normal elderly, signifying loss of orderliness of insulin secretion (P < 0.05). In response to treatment with GLP-1, insulin burst mass (P < 0.05) and pulsatile insulin secretion (P < 0.05) improved significantly in elderly patients with diabetes.

Conclusions: We conclude that alterations in pulsatile insulin release can be improved in elderly patients with diabetes by the administration of sc GLP-1.